The present invention is directed to physical structures and methods for controlling the flow of small volumes of liquids such as blood through capillary devices. The present invention is particularly directed to such structures that include curved capillary flow paths and microstructures which can be positioned in the flow path to promote uniform capillary pull around the curve. The present invention also concerns capillary channels that connect to such curved capillary flow paths.
Many diagnostic tests are carried out in the clinical field utilizing a blood sample. It is desirable, when possible, to use a very small volumes of blood, often no more than a drop or two. Capillary structures are often employed when handling such small volumes of blood or other fluids particularly in combination with electrochemical sensors. The capillary structures can be included in analyte sensing apparatus configured in the form of a disposable test strip adapted to cooperate with electrical circuitry of a testing instrument. The test strip generally includes a first defined area to which a biological fluid is to be applied. At least one capillary pathway leads from the first area to one or more second areas containing sensing apparatus such as electrodes or optical windows. Reagent chemical compositions can also be included in one or more of the capillary pathways or second areas containing the sensing electrodes. The testing instrument is A generally programmed to apply a preselected potential to the sensing electrodes at a predetermined time following application of the biological fluid to the first defined area. The current flowing between given pairs of the sensing electrodes through the biological fluid is then measured to provide an indication of the presence and/or concentration of one or more target analytes in the biological fluid. Following the testing, the test strip can be removed from the testing instrument and suitably disposed.
Some electrochemical sensors of this general type include structures intended to promote the transport of plasma, while substantially excluding or inhibiting the passage of erythrocytes to the area or areas containing the sensing electrodes. Example devices are disclosed in U.S. Pat. No. 5,658,444 and in European Patent Application 88303760.8. Other sensors include grooves and other structures designed to direct fluid flow along prescribed paths such as in U.S. Pat. Nos. 4,233,029 and 4,618,476. The test strips including such capillary pathways are generally constructed in a layered geometry as shown, for example, in U.S. Pat. No. 5,798,031.
There is a continuing need for the development of commercially feasible sensors that test for biologically significant analytes. In particular, there is a need for such sensors in which the transport of the biological fluids is controlled as it flows from one location to another. Such flow control could be useful, for example, in the development of structures for sequential or simultaneous testing of a given biological fluid sample for multiple analytes, or repeated tests of given portions of a sample for the same analyte for reliability, or to develop time variant functions of a given analyte interaction. Of particular interest is the development of structures for controlling the capillary flow of liquids in curved pathways and around corners so that the leading edge or meniscus of the fluid remains substantially perpendicular to the walls defining the capillary channel or pathway as the fluid flows toward areas containing the sensing elements and/or reagents.
A fluid transport structure of the present invention generally includes a capillary pathway having at least one curved portion. The pathway curved portion can be viewed as comprising a base, an inner wall defined by a first radius and an outer wall situated generally parallel to the inner Wall and defined by a second radius greater than the first radius. The inner wall and outer wall are fixed to the base and define the lateral boundaries of the capillary pathway. A lid extends at least from the inner wall to the outer wall to cover the capillary pathway. The capillary pathway includes apparatus facilitating the transport of a liquid longitudinally through the pathway. The apparatus generally comprises at least one group of microstructures fixed to the base that occupy entirely the capillary pathway between the inner and outer walls. The microstructures within each group are generally spaced from each other on a nearest neighbor basis by a first distance that is less than the distance necessary to achieve capillary flow of liquid. Each group of microstructures is confined to a discrete arcuate segment of the curved portion of the capillary pathway, and is spaced from any adjacent group by a distance greater than the first distance.
The microstructures can comprise a variety of shapes. A preferred shape for the microstructures is one of partitions having longitudinal dimensions about equal to the discrete arcuate segment occupied by the group. Each partition is preferably arcuate, but can also be linear, or even zig-zag. Another preferred shape for the microstructures is posts arranged in a triangular close pack configuration. Each posts can have a variety of shapes in cross-section, such as circular, diamond, square, xc2xd moon, triangle, etc. At least some of the posts adjacent to either of the walls can be joined to the walls by radial extensions. Generally, the microstructures located closer to the inner wall of the curved portion of the capillary pathway are smaller than the microstructures located closer to the outer wall. The microstructures within-each group are preferably centered on centers which are equally spaced from each other.
The fluid transport structure of the present invention can also include at least one capillary channel coupled to the capillary pathway curved portion generally between two adjacent groups of the microstructures. Fluid flow into the capillary channels is generally a function of the lateral dimensions of the capillary channels and can be controlled at least in part by the spacing of the microstructures in the capillary pathway adjacent to the capillary channels. Generally, the walls defining the lateral boundaries of the capillary channels are much closer to each other than are the inner and outer walls of the capillary pathway. To achieve differences in fill times, the walls defining the lateral boundaries of any two capillary channels are generally spaced apart by different distances.
A biological fluid handling structure according to the present invention can be molded as two or more pieces of a thermoplastic resin such as nylon, styrene-acrylic copolymer, polystyrene, or polycarbonate using known micro-injection molding processes. The mold for making the obstructions in the capillary pathway can be constructed by deep reactive ion etching processes typically employed in the manufacture of molds for pre-recorded compact disks and digital video disks. A suitable dry reagent can be situated at desired locations in the structure, if desired. The pieces of the structure are then assembled so that the capillary pathway is enclosed within the structure, yet can be accessed at an inlet port designed to receive a sample of a biological fluid. The apparatus is suitable for use with many types of fluid samples. For example body fluids such as whole blood, blood serum, urine, and cerebrospinal fluid can be applied to the apparatus. Also food products, fermentation products and environmental substances, which potentially contain environmental contaminants, can be applied to the apparatus.
The resulting structure can be viewed as an apparatus including a capillary pathway defined by a base, an inner wall and an outer wall situated generally parallel to the inner wall, the inner wall and outer wall being fixed to the base and defining lateral boundaries of the capillary pathway, and a lid extending at least from the inner wall to the outer wall covering the capillary pathway. The capillary pathway includes one or more groups of microstructures fixed to the base within discrete segments of the pathway for facilitating the transport of a liquid longitudinally through the pathway. At least two capillary channels are coupled between two adjacent groups of microstructures to either the inner and outer wall of the capillary pathway. Each capillary channel includes a pair of side walls defining lateral boundaries of each capillary channel, each pair of side walls of all capillary channels being selectively spaced from each other yet closer to each other than are the inner and outer walls of the capillary pathway, the pair of side walls of one of the capillary channels being spaced apart by a different distance than one other capillary channel. The grouped microstructures are spaced from each other within each group on a nearest neighbor basis by less than a first distance that is less than that necessary to achieve capillary flow of liquid with each group being confined to a discrete arcuate segment of a curved portion of the capillary pathway. Each group of microstructures are spaced from any adjacent group by an inter-group space greater than the width of any of the capillary channels connected to the capillary pathway. Generally, the microstructures are centered on centers which are equally spaced from each other, and microstructures that are located closer to the inner wall of any curve in the capillary pathway are generally smaller than the microstructures located closer to the outer wall. This combination of structural features causes fluids to flow through the capillary pathway so that the rate of flow is somewhat non-uniform as the fluid travels around curved portions of the capillary pathway, the meniscus appearing to momentarily pause at each inter-group space, the flow being somewhat slower near the inner wall of a curved portion than near the outer wall.
Other advantageous features will become apparent upon consideration of the following description of preferred embodiments which references the attached drawings depicting the best mode of carrying out the present invention.